Digital karyotyping

Wang, Tian‐Li; Maierhofer, Christine; Speicher, Michael R.; Lengauer, Christoph; Vogelstein, Bert; Kinzler, Kenneth W.; Velculescu, Victor E.

doi:10.1073/pnas.202610899

Cited by 208 publications

(156 citation statements)

References 24 publications

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“…The PCR conditions were as follows: denaturing at 95 1C for 10 min, followed by 40 cycles of 95 1C for 15 s and 58.5 1C for 1 min. As an internal control, Line-1 was used (Wang et al, 2002). The primers used for examination of 4q deletions are listed in Supplementary Table S3.…”

Section: Dna Quantitative Pcrmentioning

confidence: 99%

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

et al. 2008

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The Wnt signaling pathway is involved in normal embryonic development and controls the homeostatic self-renewal of stem cells in adult tissues. Constitutive activation of Wnt signaling contributes to cancer development and progression. We identified a CXXC4 homozygous deletion at 4q24 in an aggressive renal cell carcinoma (RCC) using single-nucleotide polymorphism (SNP) arrays. CXXC4 encodes Idax, which negatively regulates Wnt signaling by binding to the PDZ domain of Dishevelled. CXXC4 mRNA levels in tumor samples were significantly lower in patients with metastases compared with those without (P ¼ 0.0016). Patients whose tumors had lower CXXC4 expression than normal kidney showed a poorer cause-specific survival outcome than those with higher expression (P ¼ 0.0095). Decreased expression of CXXC4 also correlated with cytoplasmic staining of b-catenin. Knockdown of CXXC4 induced the nuclear translocation of b-catenin and altered expression of a set of genes involved in cell proliferation, invasion and survival. Furthermore, reduced expression of CXXC4 by small interfering RNAs promoted cell proliferation and inhibited apoptosis after 5-FU and doxorubicin treatment in RCC cells. These data suggest that CXXC4 plays a critical role in tumor progression of RCC through Wnt signaling. Wnt signaling could thus be a potential molecular target in RCC indicating decreased CXXC4 expression.

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Section: Dna Quantitative Pcrmentioning

confidence: 99%

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

et al. 2008

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“…The following primers were used: PIK3CA, 5 ¶-TCAGATTTACGGCAAGATATGC-3 ¶ (forward) and 5 ¶-TGCCTTACTGGTTACCTACCG-3 ¶ (reverse); Line-1, 5 ¶-AAAGCCGCTCAACTACATGG-3 ¶ (forward) and 5 ¶-TGCTTTGAATGCGTCCCAGAG-3 ¶ (reverse). Real-time PCR conditions and copy number calculations were done as described previously (27).…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

PIK3CA Gene Mutations in Pediatric and Adult Glioblastoma Multiforme

Gallia¹,

Rand²,

Siu³

et al. 2006

Molecular Cancer Research

152

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The phosphatidylinositol 3-kinases (PI3K) are a family of enzymes that relay important cellular growth control signals. Recently, a large-scale mutational analysis of eight PI3K and eight PI3K-like genes revealed somatic mutations in PIK3CA, which encodes the p110A catalytic subunit of class IA PI3K, in several types of cancer, including glioblastoma multiforme. In that report, 4 of 15 (27%) glioblastomas contained potentially oncogenic PIK3CA mutations. Subsequent studies, however, showed a significantly lower mutation rate ranging from 0% to 7%. Given this disparity and to address the relation of patient age to mutation frequency, we examined 10 exons of PIK3CA in 73 glioblastoma samples by PCR amplification followed by direct DNA sequencing. Overall, PIK3CA mutations were found in 11 (15%) samples, including several novel mutations. PIK3CA mutations were distributed in all sample types, with 18%, 9%, and 13% of primary tumors, xenografts, and cell lines containing mutations, respectively. Of the primary tumors, PIK3CA mutations were identified in 21% and 17% of pediatric and adult samples, respectively. No evidence of PIK3CA gene amplification was detected by quantitative real-time PCR in any of the samples. This study confirms that PIK3CA mutations occur in a significant number of human glioblastomas, further indicating that therapeutic targeting of this pathway in glioblastomas is of value.Moreover, this is the first study showing PIK3CA mutations in pediatric glioblastomas, thus providing a molecular target in this important pediatric malignancy.

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“…Digital karyotyping techniques (Wang et al 2002b;Tengs et al 2004) represent an approximation of total shotgun sequencing, in which a defined representation (in our case, 27-bp sequence per 4096-bp average for 6-bp recognition site, or 0.66% of total genome) can be sequenced to near-saturation. This technique has recently been used to identify microbial sequences associated with human cancers ) but has not been previously used to characterize complex microbiomes.…”

Section: Discussionmentioning

confidence: 99%

“…Several digital karyotyping methods have been used to characterize defined genomic representations (Wang et al 2002b;Tengs et al 2004;Leary et al 2007). These are capable of generating high resolution karyotypes of human DNA in analyzed samples, as well as identifying foreign DNA within the sample.…”

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confidence: 99%

Biome representational in silico karyotyping

Muthappan¹,

Lee²,

Lamprecht³

et al. 2011

Genome Res.

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Metagenomic characterization of complex biomes remains challenging. Here we describe a modification of digital karyotyping—biome representational in silico karyotyping (BRISK)—as a general technique for analyzing a defined representation of all DNA present in a sample. BRISK utilizes a Type IIB DNA restriction enzyme to create a defined representation of 27-mer DNAs in a sample. Massively parallel sequencing of this representation allows for construction of high-resolution karyotypes and identification of multiple species within a biome. Application to normal human tissue demonstrated linear recovery of tags by chromosome. We apply this technique to the biome of the oral mucosa and find that greater than 25% of recovered DNA is nonhuman. DNA from 41 microbial species could be identified from oral mucosa of two subjects. Of recovered nonhuman sequences, fewer than 30% are currently annotated. We characterized seven prevalent unknown sequences by chromosome walking and find these represent novel microbial sequences including two likely derived from novel phage genomes. Application of BRISK to archival tissue from a nasopharyngeal carcinoma resulted in identification of Epstein-Barr virus infection. These results suggest that BRISK is a powerful technique for the analysis of complex microbiomes and potentially for pathogen discovery.

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Digital karyotyping

Cited by 208 publications

References 24 publications

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

PIK3CA Gene Mutations in Pediatric and Adult Glioblastoma Multiforme

Biome representational in silico karyotyping

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